A drug-induced thyrotoxic state can be seen with excess administration of exogenous thyroid hormone. This condition usually occurs inadvertently but is sometimes intentional, as in factitious disorder or malingering.
Graves’ disease is an autoimmune disorder that occurs when antibodies (thyroid-stimulating hormone immunoglobulins) stimulate thyroid TSH receptors, increasing thyroid hormone synthesis and secretion. Graves’ disease—seen in 60% to 85% of patients with thyrotoxicosis—is the most common cause of hyperthyroidism.15
Patients most often are women of childbearing years to middle age. Exophthalmos and other eye changes are common, along with diffuse goiter. Encephalopathy can be seen in Graves’ disease and Hashimoto’s thyroiditis because the brain can become an antibody target in autoimmune disorders.
Toxic multinodular goiter consists of autonomously functioning, circumscribed thyroid nodules with an enlarged (goitrous) thyroid, that typically emerge at length from simple (nontoxic) goiter—characterized by enlarged thyroid but normal thyroid-related biochemistry. Onset is typically later in life than Graves’ disease.11,17
Thyrotoxicosis is often relatively mild in toxic multinodular goiter, with marginal elevations in T4 and/or T3. Unlike in Graves’ disease, ophthalmologic changes are unusual. Tachycardia and weakness are common (Table 2).
Nonpsychiatric symptoms seen with hyperthyroidism
|Heat intolerance (cold tolerance)|
|Weight loss (despite good appetite)|
|Goiter (enlarged thyroid gland)|
|Proximal muscle weakness/myopathy|
|Worsening or precipitation of angina, heart failure|
|Warm, moist skin|
|Velvety skin texture|
|Ruddy or erythemic skin/facial flushing|
|Premature graying (Graves’ disease)|
|Frequent bowel movements|
|Osteopenia or osteoporosis|
Adenomas. Toxic thyroid adenoma is a hyperfunctioning (“toxic”) benign tumor of the thyroid follicular cell. A TSH-secreting pituitary adenoma is a rare cause of hyperthyroidism.16
Thyroid storm is a rare, life-threatening thyrotoxicosis, usually seen in medical or surgical patients. Symptoms include fever, tachycardia, hypotension, irritability and restlessness, nausea and vomiting, delirium, and possibly coma.
Psychiatrists rarely see these cases, but propranolol (40 mg initial dose), fluids, and swift transport to an emergency room or critical care unit are indicated. Antithyroid agents and glucocorticoids are the usual treatment.
Thyrotoxic symptoms from thyroid hormone therapy. Thyroid hormone has been used in psychiatric patients as an antidepressant supplement,18 with therapeutic benefit reported to range from highly valuable19 to modestly helpful or no effect.20 In some patients thyroid hormone causes thyrotoxic symptoms such as tachycardia, gross tremulousness, restlessness, anxiety, inability to sleep, and impaired concentration.
Patients newly diagnosed with hypothyroidism can be exquisitely sensitive to exogenous thyroid hormone and develop acute thyrotoxic symptoms. When this occurs, a more measured titration of thyroid dose is indicated, rather than discontinuing hormone therapy. For example, patients whose optimal maintenance levothyroxine dosage proves to be >100 mcg/d might do better by first adapting to 75 mcg/d.
Thyroid hormone replacement can increase demand on the adrenal glands of chronically hypothyroid patients. For those who develop thyrotoxic-like symptoms, a pulse of glucocorticoids—such as a single 20-mg dose of prednisone (2 to 3 times the typical daily glucocorticoid maintenance requirement)—is sometimes very helpful. Severe eye pain and periorbital edema has been reported to respond to prednisone doses of 120 mg/d.13
Serum TSH is a sensitive screen. Low (<0.1 mIU/mL) or immeasurably low (<0.05 mIU/mL) circulating TSH usually means hyperthyroidism. A TSH screen is not foolproof, however; very low TSH can be seen with low circulating thyroid hormones in central hypothyroidism or in cases of laboratory error.
The recommended routine initial screen of the pituitary-thyroid axis in psychiatric patients includes TSH, free T4, and possibly free T3.3 Suppressed TSH with high serum free T3 and/or free T4 (accompanied by high total T4 and/or T3) is diagnostic of frank biochemical hyperthyroidism. If circulating thyroid hormone concentrations are normal, hyperthyroidism is considered compensated or subclinical. Although only free thyroid hormones are active, total T4 and total T3 are of interest to grossly estimate thyroid hormone output.
When you identify a thyrotoxic state, refer the patient for an endocrinologic evaluation. Antithyroid antibodies are often positive in Graves’ disease, but anti-TSH antibodies (which can be routinely ordered) are particularly diagnostic. If thyroid dysfunction is present—especially if autoimmune-based—screening tests are indicated to rule out adrenal, gonadal, and pancreatic (glucose regulation) dysfunction.
Ms. B: Hyperthyroidism and mood
Ms. B, age 35, an energetic clerical worker and fitness devotee, developed severe insomnia. She slept no more than 1 hour per night, with irritability, verbal explosiveness, “hot flashes,” and depressed mood. “Everything pisses me off violently,” she said.
She consulted a psychiatrist and was diagnosed with major depression. Over a period of years, she was serially prescribed selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and older-generation sedating agents including trazodone and amitriptyline. She tolerated none of these because of side effects, including dysphoric hyperarousal and cognitive disruption.